Function of protein kinase C (PKC) in the regulation of apoptosis related hyperglycemia in vascular smooth muscle cells.

蛋白激酶 C (PKC) 在调节血管平滑肌细胞凋亡相关高血糖中的功能。

• 批准号: 12671105
• 负责人: YAMAMOTO Mayumi
• 金额: $ 2.05万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671105/
• 关键词: atherosclerosis; diabetes; PKC; apoptosis; apoptosis related protein; cell cycle; Western blot; flowcytometry; 動脈硬化症; アポトーシス調節蛋白; スローサイトメトリー; プロティンチナーゼC(PKC); ウェスタンブロット

Atherosclerosis is accelerated by the coexistence of diabetes mellitus. Hyperglycemia is an important etiologic factor in the development of vascular complications.(1) Effect of high glucose on cell proliferation and apoptosis in vascular smooth muscle cells (VSMC).High glucose stimulated cell proliferation and suppressed induction of apoptosis significantly in VSMC.(2) Effect of overexpression of PKC isozyme on cell proliferation and apoptosis in VSMC.Overexpression of PKC-βI stimulated cell proliferation and inhibited apoptosis expression in VSMC.In contrast, Overexpression of PKC-βII inhibited cell proliferation and increased induction of apoptosis in VSMC.(3) Effect of high glucose on the expression of PKC isozymes and apoptosis-related proteins, Bcl-xL and Bfl-1/A1.Treatment with a high glucose caused a significant decrease in apoptosis in CASMC compared with the same cells treated with a physiologically normal glucose concentration. Treatment of CASMC with high glucose concentration markedly increased mRNA expressions of bcl-xL and bfl-1/A1 compared with cells treated with normal glucose. High glucose suppressed apoptosis via upregulation of bcl-xL and bfl-1/A1 levels. High glucose-induced increase in the expression of antiapoptotic proteins may be important in the development of atherosclerosis in diabetic patients.

糖尿病的共存会加速动脉粥样硬化。高血压是血管并发症发生的重要病因。(1)高糖对血管平滑肌细胞（VSMC）增殖和凋亡的影响高糖刺激VSMC增殖，抑制VSMC凋亡。(2)PKC同工酶过表达对VSMC细胞增殖和凋亡的影响PKC-βI过表达促进VSMC细胞增殖，抑制凋亡表达，而PKC-βII过表达抑制VSMC细胞增殖，诱导凋亡增加。(3)高糖对PKC同工酶及凋亡相关蛋白Bcl-xL和Bfl-1/A1表达的影响。高糖处理可显著降低CASMC的凋亡率。高糖处理的CASMC中bcl-xL和bfl-1/A1 mRNA的表达较正常葡萄糖处理的细胞明显增加。高糖通过上调bcl-xL和bfl-1/A1水平抑制细胞凋亡。高糖诱导的抗凋亡蛋白表达增加可能在糖尿病患者动脉粥样硬化的发展中起重要作用。

项目成果

Sakuma H., Yamamoto M., Okumura M.et al.: "High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1"Am J Physiol Cell Physiol. 283. C422-C428 (2002)

Sakuma H.、Yamamoto M.、Okumura M.等人：“高葡萄糖通过增加 bcl-xL 和 bfl-1/A1 抑制人冠状动脉平滑肌细胞的凋亡”Am J Physiol Cell Physiol。

Sakuma H., Yamamoto M, et al.: "High glucose-induced Suppression of apoptosis mediated by alteration of Bcl-z family expressions in human coronary artery smooth muscle cells"Acta Sch Med GIFU. 50. 1-9 (2002)

Sakuma H.、Yamamoto M 等人：“通过改变人冠状动脉平滑肌细胞中 Bcl-z 家族表达介导的高葡萄糖诱导的细胞凋亡抑制”Acta Sch Med GIFU。

Patel N.A., Yamamoto M., Illingworth P., Mancu D., Mebert K., Chappell D.S., Watson J.E., Cooper D.R.: "Phosphoinositide 3-kinase mediates PKC-βII mRNA destabilization in vascular smooth muscle cells exposed to high glucose"Arch Biochem Biophys. 403. 111-

Patel N.A.、Yamamoto M.、Illingworth P.、Mancu D.、Mebert K.、Chappell D.S.、Watson J.E.、Cooper D.R.：“磷酸肌醇 3-激酶介导暴露于高葡萄糖的血管平滑肌细胞中 PKC-βII mRNA 不稳定”Arch生物化学生物物理学。403。111-

Okumura M., Yamamoto M., Sakuma H.et al.: "Leptin and high glucose stimulate cell proliferation in MCF7 human breast cancer cells reciprocal involvement of PKCa and PPARg expression"Biochimica et Biophysica Acta. 1592. 107-116 (2002)

Okumura M.、Yamamoto M.、Sakuma H.等人：“瘦素和高葡萄糖刺激 MCF7 人乳腺癌细胞中的细胞增殖，相互参与 PKCa 和 PPARg 表达”Biochimica et Biophysicala Acta。

Mayumi Yamamoto: "Possible involvement of the change of PKCα expression in exptim and glucose-induced cell proliteration in drug sensitive human breast cancer cells (MCF7) not in malty-drug resistant cells (MCF/ADR)."Career Detection and Revention. 24(Sup

Mayumi Yamamoto：“PKCα 表达的变化可能与药物敏感性人乳腺癌细胞 (MCF7) 而非麦芽耐药细胞 (MCF/ADR) 中的 exptim 和葡萄糖诱导的细胞增殖有关。”职业检测和预防 24。 （苏普